The present invention relates to a therapeutic agent for lower urinary tract disease, especially for interstitial cystitis.
Lower urinary tract disorder is a general term for dysfunction of lower urinary tract. Lower urinary tract symptoms, which are those resulting from lower urinary tract disorder, are mainly classified into three categories: urine storage symptoms (pollakiuria, feeling of urinary urgency and the like), urinary symptoms (decreased urinary spontaneity, splitting of urinary stream and the like), and post urinary symptoms (feeling of residual urine, dribbling after urination and the like). Further, lower urinary tract symptoms include lower urinary tract pains such as urodynia, cystalgia and urethral pain; overactive detrusor muscle; dysuria and the like. Hematuria may also be observed for lower urinary tract disorder. Diseases responsible for lower urinary tract disorder (lower urinary tract diseases) include prostatic hyperplasia, prostatitis, prostatism, bladder neck sclerosis, overactive bladder, chronic cystitis, interstitial cystitis, bladder pain syndrome and the like.
Among these, in particular, interstitial cystitis is intractable disease which is manifested by symptoms such as pollakiuria, uresiesthesia, feeling of urinary urgency, bladder discomfort and cystalgia, but shows neither urinary tract infection nor other clear pathological conditions. Although more women are affected, this disorder is developed regardless of sex and age. The number of patients is estimated to be 250,000 or more in Japan and one million or more in U.S. However, international consensus has not yet been reached with regard to the definition and diagnostic criteria of interstitial cystitis. Interstitial cystitis may also be called bladder pain syndrome (BPS) or hypersensitive bladder syndrome (HBS).
Further, chronic nonbacterial prostatitis (non-bacterial chronic prostatitis), which represents a condition in which chronic inflammation in prostate gland continues, accounts for 90% of chronic prostatitis. In many cases, it occurs in conjunction with interstitial cystitis, causing dull pain and discomfort in the scrotal position and the like or urinary symptoms such as pollakiuria, painful urination and feeling of residual urine. It is similar to interstitial cystitis in it shows symptoms such as pain before and after ejaculation and the like. The cases of chronic nonbacterial prostatitis are limited to males, but the number of the patients is said to be 700,000 to 1 million, which is greater than that of interstitial cystitis.
Possible causes of interstitial cystitis and non-bacterial chronic cystitis include activation of mast cells, abnormal glycosaminoglycan layer, urothelial cell growth inhibition, autoimmunity, neurogenic inflammation, nitric oxide metabolism, toxic substance, hypoxia and the like. Nonetheless a clear cause has not yet been known.
Although interstitial cystitis is often accompanied by nonspecific chronic inflammation in bladder, anti-inflammatory agents such as steroid do not show efficacy in the disease and an animal model of the disease. This suggests that inflammation itself has not caused the symptoms such as pollakiuria in the disease. Yet unknown causes of these diseases make it difficult to develop therapeutic agents. Agents currently used for treatment include antihistamine, antidepressant, cimetidine, antibiotics, steroid, pentosan polysulfide and the like, all of which are for symptomatic treatment and do not serve as effective treatment methods. Only suplatast tosilate has been a potentially etiotropic substance, but its efficacy remains unsatisfactory.
As described above, unlike other cystitis, use of antibiotics and antimicrobial agents do not show efficacy for interstitial cystitis. Despite severe pain associated with interstitial cystitis, there is no useful therapeutic agent at present, and in some cases, there is no choice but to remove the bladder eventually. Therefore, many patients are left to live a significantly difficult day-to-day life because of these symptoms.
For information, one of the present inventors, Tomohiro UEDA has been recognizing that interstitial cystitis in itself is also difficult to be diagnosed, and involves severe pain. Accordingly, in order to ease burden of patients suffering from interstitial cystitis, he has invented: a catheter for diagnosing interstitial cystitis connectable to an electric current perception threshold testing system (CPT system) when in use, which allows intravesical diagnose upon insertion into urethra (U.S. Pat. No. 7,338,480); a method for diagnosing interstitial cystitis (U.S. Pat. No. 8,010,185); a device of protecting urethra for use in diagnosing interstitial cystitis (Japanese Patent No. 5175988) and the like. However, as described above, a useful therapeutic agent is not available.